1. Field of the Invention
This invention relates to nerve tissue stimulation and infusion techniques, and more particularly relates to such techniques for treating anxiety disorders, including generalized anxiety disorder, obsessive-compulsive disorders, panic attacks and phobias.
2. Description of the Related Art
Some people suffer from chronic intractable anxiety disorders. The key feature of anxiety disorders is the frequent occurrence of the symptoms of fear; arousal, restlessness, heightened responsiveness, accelerated heart beat, elevated blood pressure, sweating, a desire to run or escape and avoidance behavior. Generally, anxiety is a normal response to certain life situations and can be beneficial to the person experiencing it. However, excessive or inappropriate anxiety can be detrimental. Anxiety disorders are the most common psychiatric disorders, affecting between 10 to 30 percent of the general population (Robins et. al., Arch Gen Psychiatry 1984; 41:949-958). These disorders include generalized anxiety, phobias, panic attacks, and obsessive-compulsions.
Generalized anxiety is characterized by unrealistic or excessive worry, lasting long periods of time (i.e. months). The symptoms of generalized anxiety are excessive muscle tension; overactivity in the autonomic nervous system evidenced by shortness of breath, sweating, cold hands, hyperventilation and tachycardia; and increased vigilance manifest as an increased startle response or difficulty in concentrating. Generalized anxiety is treated with oral medications from the benzodiazepine category such as chlordiazepoxide (Librium.RTM.) and diazepam (Valium.RTM.). These drugs have been shown to act by enhancing the activity of GABA.sub.A receptors leading to a hyperpolarization of neurons. The specific neurons affected are believed to be located in the amygdala which is part or the limbic system, a subset of the brain thought to be of central importance for emotional behavior.
In contrast to generalized anxiety, panic attacks are brief, recurrent episodes of terror. The symptoms include tachycardia, a feeling of "shortness of breath" that leads to hyperventilation (which can lead to unconsciousness), dizziness, trembling, flushes or chills, chest pain and a fear of dying or of going crazy or of doing something uncontrolled. Persons suffering from panic attacks may also experience generalized anxiety anticipating the occurrence of a panic attack. Finally, for some persons the occurrence of panic attacks may be associated with specific situations in which the panic attacks have occurred in the past. This association may become so strong that the person rigidly avoids the situation associated with the panic attacks. This results in the third component of the panic disorder cascade, a phobia for the situation.
A phobic reaction is a neurotic disorder characterized by an intense, persistent fear of some object or situation in which the fear is out of proportion to any real danger, is inconsistent with the persons general personality, is consciously recognized as unfounded, and frequently interferes with the patient's activities. The person may experience all the symptoms of anxiety described above. Phobias can include fear of places such as agoraphobia (fear of open spaces), acrophobia (fear of heights), achluophobia (fear of darkness) or potamophobia (fear of lakes). Alternatively, the phobia may represent a fear of a loss of control such as the fear of infection (molysmophobia) or lightning (astraphobia). In phobias, the person's anxiety is fixed to some symbolic object or situation, so that the anxiety may be controlled by avoiding the feared object or situation. The origin of the anxiety may be conscious or unconscious.
Obsessive-compulsive disorder (OCD) is a relatively frequent anxiety disorder characterized by the presence of intrusive and senseless ideas, thoughts, urges, and images (obsessions), as well as by repetitive cognitive and physical activities that are performed in a ritualistic way (compulsions) usually in an attempt to neutralize anxiety caused by obsession (American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, D.C.: American Psychiatric Association, 1994.) Examples of obsessive-compulsions are a compulsive washing of the hands or counting or ruminating about disease or sexual behavior perhaps manifest as repeated testing for AIDS. The symptoms are often concealed from others with the rituals confined to private hours but can become disruptive to school or work as the ability to control the rituals fades.
Neuroscientists are beginning to understand the neural circuitry of the brain that controls anxiety. The structures of the brain involved include the limbic system, the frontal lobes of the cortex, parts of the thalamus and basal ganglia, the locus coeruleus, dorsal raphe nucleus and the white mater connections between them such as the internal capsule and cingulum. While the general areas involved are beginning to be recognized, much is unknown about the specific functions of the areas and the nature of the signals between them.
Neurosurgeons have achieved success treating chronic intractable anxiety disorders by creating surgical lesions at specific locations in this circuitry. Procedures that have been tried and found to be at least partially successful include anterior capsulotomy, cingulotomy, subcaudate tractotomy, and a combination of the cingulotomy and subcaudate tractotomy called a limbic leucotomy. For the most part these surgical procedures result in a destruction of the fiber pathways connecting various regions of the nervous system included in the list given above. Laiteinen and Singounas (Applied Neruophysiol, 51(6):317-323, November-December 1988) tried brief stimulation intraoperatively with three to six second trains of 60 pulses per second monophasic pulses. This stimulation was applied with the patient awake at the lesion targets of the anterior limb of the internal capsule, middle anterior cingulum, rostral cingulum or the knee of the corpus callosum just prior to carrying out the lesion. Of twenty patients stimulated, three reported reduced anxiety and one reported an increase in anxiety. Electrical stimulation of nerve cells to activate them has been practiced nearly since the discovery of electricity. Benabid (The Lancet, Vol. 337, 403-406, Feb. 16, 1991) and Andy (Appl. Neurophysiol. 46, 107-111 1983 have shown more recently that stimulation of nerve cells in certain nuclei such as the ventral lateral thalamus, subthalamic nucleus, and internal segment of the globus pallidus at higher pulse frequencies can have the same effect as a functional lesion. This technique has been used to treat certain movement disorders.
Focal release of pharmaceutical agents through infusion pumps is used to treat pain and spasticity. Rise and Elsberry have proposed using infusion pumps to deliver pharmaceuticals focally to treat movement disorders as disclosed in U.S. Pat. No. 5,832,932 "Method Of Treating Movement Disorders By Brain Infusion" Nov. 10, 1998), and Rise and Ward have proposed focal delivery of medications to treat Epilepsy as disclosed in U.S. Pat. No. 5,713,923 "Techniques For Treating Epilepsy By Brain Stimulation And Drug Infusion" (Feb. 3, 1998). Abeschier (WO 94/01166) has proposed as a method to treat disorders of movement and epilepsy by using encapsulated cells which secrete neuroinhitory agents or polymer matrices loaded with neuroinhibitory agents.
Smulevich et. al. ("Psychotropic drug therapy using maintenance dosage pumps" Nevropathol Psikhiatr 1987, 87 (6) p888-93, Issn 0044-4588) have used an implantable pump for subcutaneous delivery of psychotropic drugs. They found this technique particularly useful when providing " . . . functional training of patients with phobic abnormalities."